Control of Respiration

Control of Respiration Bioengineering 6000 CV Physiology

Central Control of Ventilation

• Goal: maintain sufficient ventilation with minimal energy
– Ventilation should match perfusion
• Process steps:
– Ventilation mechanics + aerodynamics
• Points of Regulation
– Breathing rate and depth, coughing, swallowing, breath holding
– Musculature: very precise control
• Sensors:
– Chemoreceptors: central and peripheral
– Stretch receptors in the lungs, bronchi, and bronchioles
• Feedback:
– Nerves
– Central processor:
• Pattern generator of breathing depth/amplitude
• Rhythm generator for breathing rate

Control of Respiration Bioengineering 6000 CV Physiology

 Peripheral Chemosensors

• Carotid and Aortic bodies

• Sensitive to PO2, PsCO2,
and pH (CO2 sensitivity may
originate in pH)
• Responses are coupled
• Adapt to CO2 levels
• All O2 sensing is here!
• Carotid body sensors more
sensitive than aortic bodies

Control of Respiration Bioengineering 6000 CV Physiology

O2 Sensor Details

• Glomus cells
• K-channel with O2 sensor
• O2 opens channel and
hyperpolarizes cell
• Drop in O2 causes reduction in
K current and a depolarization
• Resulting Ca2+ influx triggers
release of dopamine
• Dopamine initiates action
potentials in sensory nerve

Control of Respiration Bioengineering 6000 CV Physiology

 Central CO2/pH Chemoreceptors
• Sensitive to pH in CSF
• CSF poorly buffered
• H+ passes poorly through BBB
but CO2 passes easily
• Blood pH transmitted via CO2
to CSF
• Adapt to elevated CO2 levels
(reduced pH) by transfer of
HCO3- or Cl- into CSF (slow)
• Stimulation of this system
causes urge to breath.

Control of Respiration Bioengineering 6000 CV Physiology

Innervation of Respiratory System

Constriction
Dilation
Inspiration

Control of Respiration Bioengineering 6000 CV Physiology

Central Control
Overview

Control of Respiration Bioengineering 6000 CV Physiology

Pattern Control Mechanisms

• Phrenic nerve carries
stimulus to diaphragm and
determines breathing
pattern
• Rise in CO2 increases
phrenic nerve activity
• Rise in stretch pulmonary
stretch receptors suppress
phrenic nerve activity

Control of Respiration Bioengineering 6000 CV Physiology

 Rate Control Mechanisms
• Mechanism of pacemaker not known
• Rhythm is function of previous breath:
– The deeper the breath, the lower the rate
– Stretch receptors sense inspiration
– Inspiratory/expiratory durations are the same
– Breathing is continuous while awake
• Inspiratory impulses dominate:
– Expiratory stimulation is constant
– Inspiratory stimulation superimposed and inhibits expiratory
• Sleep:
– Breathing is episotic
– Central drive reduced so peripheral chemoreceptors stimulate
based on O2 and CO2 levels

Control of Respiration Bioengineering 6000 CV Physiology

Other Ventilation Factors

• Lung inflation: stretch receptors decrease inflation
– CO2 suppresses them
• Irritant receptors in the lung: cause bronchioconstriction and coughing
• J-receptors: sense interstitial fluid changes (edema)
– Cause sense of breathlessness
• Emotional state; sympathetic stimulation cause vasoconstriction in
peripheral sensors and increases response
• Temperature: stimulates peripheral sensors
• Exercise: increase sensitivity of chemoreceptors, probably through
catecholamines
• Speech: inhale before speaking
• Conscious control

CO2 is the dominant control factor!

PO2 must drop to 60 mm Hg (3000 m) before it triggers change

Control of Respiration Bioengineering 6000 CV Physiology

 Ventilation/Perfusion (V/Q) Matching
• Goal:
– Match blood flow to ventilation, both local and
global
• Process:
– Q regulated to match tissue needs and V
regulated for adequate supply In healthy humans at
rest V/Q is roughly
– V and Q vary with weight but ratio roughly 0.8, 0.8
rises with exercise
• Sensors:
– Local, at the tissue levels
• Actuators
– Vascular/bronchial dilation and constriction,
shunting
– Local drop in V cause hypoxia, which inhibits K+
channels and causes smooth muscle constriction,
increase in Rv; (opposite from systemic
circulation)
– Local drop in Q results in drop in CO2, which
drops H+ and causes constriction of airway
• Feedback
– local

Control of Respiration Bioengineering 6000 CV Physiology

Pulmonary Circulation

• Balance among
– PA (alveolar pressure) Low blood flow
– Pa (arterial pressure)
– Pv (venous pressure)
• Pulmonary circulation
– lower pressure (22/7.5
mm Hg)
– lower filtration of H20
– extensive lymphatics
• Lungs surround heart and
minimize variations with
posture
High blood flow

Control of Respiration Bioengineering 6000 CV Physiology

 Breath Holding

Control of Respiration Bioengineering 6000 CV Physiology

What Did Leonardo Get Wrong?

Control of Respiration Bioengineering 6000 CV Physiology

 Underwater Breathing
• Gas Physics
– Pressure increases by 1 atm each 10 m
– Air pressure at Everest 1/3 of normal, water pressure at same
depth = 885 times normal
• Diving
– Fixed volume in lungs compresses with depth
– Snorkel breathing limited to about .5 m
– More depth requires pressurized air
– Body initially more buoyant than water; with depth, gas
compresses and density increases and buoyancy decreases
– Dive and apnea records: http://www.aidainternational.org)
– Breath-hold record: ??

Control of Respiration Bioengineering 6000 CV Physiology

2014 Records

http://www.aidainternational.org/competitive/worlds-records
Control of Respiration Bioengineering 6000 CV Physiology
 Ciasson Disease

Eads Bridge, St. Louis, MO. 1874.

15 died, 79 severely afflicted by bends

Control of Respiration Bioengineering 6000 CV Physiology

Caisson Disease

Control of Respiration Bioengineering 6000 CV Physiology

 Bends and other Woes

• Pressure drives more gasses into blood,

e.g., 1 l of nitrogen per 10 m
• Resurfacing too quickly causes bubbles to form and
grow (opening carbonated drink)
• Bubbles in capillaries, joints, inner ear, brain
• Discovered in 1878 among “Caissons” workers
• Whales and seals
– Dive deeply (to 1570 m) but no bends
– Breath out before diving, lungs empty and collapse
– No gas dissolved into the blood

Control of Respiration Bioengineering 6000 CV Physiology

The Physiology of Altitude

HOW?

Control of Respiration Bioengineering 6000 CV Physiology

 The Challenges of Altitude
• At sea level
– Total pressure: 760 mm Hg (Torr)
– PO2: 20% * 760 = 150 mm Hg in air, 100 mm Hg in lungs
– Water vapor: 47 mm Hg = 6%
• At 5800 m
– Highest permanent habitation
– PO2 = 80 mm Hg
• At Everest summit (8848 m)
– Total pressure: estimated as 230, really 253 mmHg
– Water vapor: 47 mm Hg = 18.6%
– PO2: 21% = 43 (calculated) 35 (measured) in alveoli mmHg
• At 12,000 m
– Even with pure O2, PO2 drops below 100 mmHg

Control of Respiration Bioengineering 6000 CV Physiology

How High Can We Go?

“Those who, like Major Godwin-Austen, have had all the advantages of
experience and acclimatization to aid them in attacks upon the higher
Himalayas agree that 21,500 feet (7,050 m) is near the limit at which
man ceases to be capable of the slightest further exertion.”
T.W. Hanchliff, President British Alpine Society 1876

It is “unlikely that the mountain could be climbed without oxygen

equipment without serious risk”
LGCH Pugh , J. Physiology, 1958

“Now, when... I have nothing more to do than breathe, a great peace

floods my whole being. I breathe like someone who has run the race of
his life and knows that he may now rest forever... In my state of spiritual
abstraction, I no longer belong to myself and to my eyesight. I am
nothing more than a single, narrow, gasping lung, floating over the
mists and the summits”
Reinhold Messner, 1979

Control of Respiration Bioengineering 6000 CV Physiology

 Response to Altitude I

Cardiac Consequences??
output

Ventilation Ventilation
Increased
affinity
PO2 PO2

PCO2

pH pH

O2 Affinity

Stimulate O2 Stimulate Opposing

sensors ventilation stimuli.
Left shift of O2
dissociation

Control of Respiration Bioengineering 6000 CV Physiology

Response to Altitude II

Ventilation Ventilation

PO2 PO2

pH Excretion
of HCO3- pH

Reduced
affinity

O2 Affinity DPG O2 Affinity

Opposing Elevated
stimuli. ventilation
Left shift of O2 Right shift of O2
dissociation dissociation

Control of Respiration Bioengineering 6000 CV Physiology

 Response to Altitude III

Cardiac Cardiac
output output

Ventilation Ventilation Ventilation Ventilation

PO2 PO2 PO2 PO2

Stimulate O2 Excretion Reduced CO2

sensors PCO2 of HCO3- sensitivity
pH pH PCO2
pH pH
O2 Affinity
O2 Affinity O2 Affinity
(Left shift)
(DPG mediated
right shift) RBC’s &
blood volume

Control of Respiration Bioengineering 6000 CV Physiology

Long Term Response

• Increase in hematocrit (erythropoietin)
• Increase in vascularization (growth factors)
• Rise in blood volume (by 1/3)
• Cardiac output normal
• Local pulmonary vasoconstriction
– Rise in pulmonary pressures
– More even distribution of pulmonary perfusion
• Altered growth: small and barrel chested
– High lung to body volume ratio
– Right ventricular hypertrophy
• Range of responses
– Mountain sickness more common among Andeans than
Tibetans
– Birds routinely fly to 6000 m in migration, some fly over the
Himalaya (9000 m)
Control of Respiration Bioengineering 6000 CV Physiology
 Gas Transport Requirements

(100 mm Hg
in lungs)

In maximal exercise, what is the

• Ventilation rate limiting step?
• Diffusion from/to
respiratory system
• Bulk transport Oxygen transport in the blood!
• Diffusion to/from tissue

Control of Respiration Bioengineering 6000 CV Physiology